Functional Impairment of Blood-Brain Barrier Following Pesticide Exposure during Early Development in Rats
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1. The effect of certain pesticides on the functional integrity of the developing blood-brain barrier (BBB) was studied following single and repeated exposure, and after subsequent withdrawal in rats. 2. Ten-day-old rat pups exposed orally to quinalphos (QP, organophosphate), cypermethrin (CM, pyrethroid) and lindane (LD, organochlorine) at a dose of 1/50th of LD50, showed a significant increase in the brain uptake index (BUI) for a micromolecular tracer, sodium fluorescein (SF), by 97, 37 and 72%, respectively, after 2 h. Residual increases in the BUI were found even after 3 days of the single treatment of QP (28%) and LD (23%). 3. Repeated exposure for 8 days (postnatal days (PND) 10-17) with QP, CM and LD increased the BBB permeability by 130, 80 and 50%, respectively. Recovery from these changes was complete in QP and LD-treated animals after 13 days (PND 18-30) of withdrawal. However, CM showed persistent effects that were normalized only after 43 days (PND 18-60) of withdrawal. 4. A single dose reduced to 1/100th of LD50 also increased BUI in 10-day-old rat pups following QP (20%) and CM (28%) exposure at 2 h. 5. An age-dependent effect of these pesticides was evident from the study showing higher magnitude of BUI changes in 10-day-old rats as compared to that in 15-day-old rats. Furthermore, adult rats did not show any effect on BBB permeability even at a higher dose (1/25th of LD50) of these pesticides given alone or in combination with piperonyl butoxide (600 mg/kg, i.p.) for 3 consecutive days. 6. This study showed that developing BBB is highly vulnerable to single or repeated exposure of certain pesticides. The observed persistent effects during brain development even after withdrawal of the treatment may produce some neurological dysfunction at later life as well.
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Blood-brain barrier integrity can be compromised by exposures to certain toxicants and by health conditions through molecular alterations in barrier function.
“Integrity of the BBB can be compromised because of exposures to certain toxicants, such as pesticides, mixed vehicle emissions, and tobacco smoke, as well as certain health conditions including diabetes and neurological disorders reviewed in Neurotoxicity of PFAS in Sensitive Populations, through molecular alterations in barrier function (Gupta et al., 1999; Weiss et al., 2009; Mazzone et al., 201”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Gupta et al., 1999
The Discussion reports increased blood–brain barrier permeability after pesticide exposure in developing rat pups, supporting the pesticide portion of the claim. It does not establish that molecular alterations caused the impairment; the study measured permeability rather than a molecular mechanism. The other exposures and health conditions in the citing sentence are not specifically attributed to this source. (LLM, conf=0.85)
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- Authors
- Gupta, A., Agarwal, R., & Shukla, G. S.
- Affiliations
- Indian Institute of Toxicology Research (IN)
- Venue
- Human & Experimental Toxicology
- Publisher
- SAGE Publications
- Published
- 1999-03
- Volume
- 18
- Issue
- 3
- Pages
- 174-179
- ISSN
- 0960-3271 (ISSN-L)
- 1477-0903
- OpenAlex
- W2046138936
- Cited by
- 85
- References
- 32
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 5
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human & Experimental Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research, India
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- blood-brain barrier, pesticide exposure, quinalphos, cypermethrin, lindane, organophosphate insecticides, pyrethroid insecticides, organochlorine insecticides, brain uptake index, fluorescein, developmental neurotoxicity, postnatal development, piperonyl butoxide, pesticide withdrawal, age-dependent effects
- MeSH terms
- Administration, Oral, Aging, Animals, Animals, Newborn, Hexachlorocyclohexane, Blood-Brain Barrier, Body Weight, Brain, Capillary Permeability, Female, Insecticides, Lethal Dose 50, Organothiophosphorus Compounds, Pregnancy, Pyrethrins, Rats
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